title: Polymorphisms of folate metabolism-related genes and survival of patients with colorectal cancer in the Korean population.
abstract: BACKGROUND
  5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival.
  
  
  METHODS
  We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C>T and 1298A>C, and RFC1 -43T>C, 80G>A, and 696C>T. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS).
  
  
  RESULTS
  The combined TS 1494 0bp6bp+6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 -43CC and 80AA genotypes were associated with favorable OS.
  
  
  CONCLUSIONS
  Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings.
authors.affiliation: Department of Internal Medicine, School of Medicine, CHA University, Seongnam, South Korea.
authors.forename: Moon Ju
authors.initials: MJ
authors.lastname: Jang
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: So Young
authors.initials: SY
authors.lastname: Chong
authors.forename: Sung Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Doyeun
authors.initials: D
authors.lastname: Oh
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Cho
authors.forename: Young Geon
authors.initials: YG
authors.lastname: Ji
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics; D058978:Reduced Folate Carrier Protein / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; D005472:Fluorouracil
keywords: 5-FU; 5-fluorouracil; CI; CRC; Colorectal cancer; HR; MTHFR; Methylenetetrahydrofolate reductase (MTHFR); OS; RFC1; RFS; Reduced folate carrier 1 (RFC1); Survival; TS; TSER; Thymidylate synthase (TS); colorectal cancer; confidence interval; hazard ratio; methylenetetrahydrofolate reductase; overall survival; reduced folate carrier 1; relapse-free survival; thymidylate synthase; thymidylate synthase enhancer region